Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

The foodborne pathogen enterohemorrhagic Escherichia coli (EHEC) results in severe diarrheal disease and causes significant morbidity and mortality worldwide. In Canada, EHEC causes an estimated 50 000 infections per year, numerous deaths, and a heavy financial burden. EHEC outbreaks in Canada - such as the Walkerton epidemic and the current outbreak from contaminated XL Foods, Inc. beef - highlight the relevance of this pathogen to Canadian health. The proposed study aims to understand how human cellular functions are influenced and disrupted by EHEC infection. This understanding is vital to prevent and treat future infections. Studying how human proteins are altered during infection (the "proteomics" of infection) can further our understanding of how EHEC affects entire protein networks and cause disease, as well as how human cells respond to infection. TAILS (terminal amine isotopic labeling of substrates) is a new proteomics technique that not only identifies and quantifies human proteins but also characterizes how they have been modified (i.e. fragmentation or the addition of chemical groups). The proposed research will use TAILS to study EHEC infection of human cells cultured in Petri dishes to see how human protein networks have been altered. I hypothesize that altered human proteins are important during infection and that their study will provide valuable insight into the molecular and system-wide mechanisms by which EHEC causes human disease. This research involves a strong collaboration between the TAILS developers and one of the leading Canadian research groups studying EHEC, bacterial pathogenesis, and host-pathogen interactions, forming a uniquely capable group for this project. This study has applications to the fields of cell biology, molecular microbiology and immunology, examining how enteric bacterial pathogens cause human disease and how human cells respond to infection. This study could also reveal clinical targets against pathogenic E. coli.